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Willie O Pinheiro,1,2 Maria L Fascineli,1 Gabriel R Farias,1 Frederico H Horst,1 Laise Rodrigues de Andrade,1 Luis Henrique Corrêa,3 Kelly Grace Magalhães,3 Marcelo Henrique Sousa,4 Marcos C de Almeida,1 Ricardo B Azevedo,1 Zulmira GM Lacava1,2 1Department of Genetics and Morphology, Institute of Biological Sciences, CNANO, University of Brasilia, Brasilia, DF 70910-900, Brazil; 2Post-graduation Program in Molecular Pathology, Faculty of Medicine, University of Brasilia, Brasília, DF 70910-900, Brazil; 3Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasilia, DF 70910-900, Brazil; 4Green Nanotechnology Group, Faculty of Ceilandia, University of Brasilia, Brasília, DF 72220-900, Brazil Background: Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose: To fill part of this gap, this work aimed to investigate biocompatibility and biodistribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods: NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results: NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion: Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals’ age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population. Keywords: elderly, nanotoxicity, maghemite nanoparticles, superparamagnetic iron oxide nanoparticles, SPIO, nano-safety, inductively coupled plasma optical emission spectrometry, ICP-OES